USPTO Patents Application 10595161

United States Patent and Trademark Office

UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office

Address: COMMISSIONER FOR PATENTS
P.O. Box 1450

Alexandria, Virginia 223 1 3- 1 450
www.uspto.gov

APPLICATION NO.

FILING DATE

FIRST NAMED INVENTOR

ATTORNEY DOCKET NO. |

CONFIRMATION NO.

10/595,161

03/10/2006

Mark Jozef Albert Waer

50304/114001

3570

21559 7590

CLARK & ELBING LLP
101 FEDERAL STREET
BOSTON, MA 021 10

02/12/2008

EXAMINER

HUGHES, ALICIA R

ART UNIT

PAPER NUMBER

1614

NOTIFICATION DATE

DELIVERY MODE

02/12/2008 ELECTRONIC

Please find below and/or attached an Office communication concerning this application or proceeding.

The time period for reply, if any, is set in the attached communication.

Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the

following e-mail address(es):

patentadministrator@clarkelbing.com

PTOL-90A (Rev. 04/07)

Office Action Summary

Application No.

10/595,161

Applicant(s)

WAER ET AL.

Examiner

Alicia R. Hughes

Art Unit
1614

7/, e MAILING DATE of this communication appears on the cover sheet with the correspondence address
Period for Reply

A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,
WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.

- Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed
after SIX (6) MONTHS from the mailing date of this communication.

- If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.

- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 1 33).
Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
earned patent term adjustment. See 37 CFR 1 .704(b).

Status

1 )[3 Responsive to communication(s) filed on 10 March 2006 .
2a)D This action is FINAL. 2b)^ This action is non-final.

3) Q Since this application is in condition for allowance except for formal matters, prosecution as to the merits is

closed in accordance with the practice under Ex parte Quayle, 1935 CD. 1 1 , 453 O.G. 213.

Disposition of Claims

4) S Claim(s) 8-27 is/are pending in the application.

4a) Of the above claim(s) is/are withdrawn from consideration.

5) D Claim(s) is/are allowed.

6) ^ Claim(s) 8-27 is/are rejected.

7) D Claim(s) is/are objected to.

8) D Claim(s) are subject to restriction and/or election requirement.

Application Papers

9) D The specification is objected to by the Examiner.

10)IEI The drawing(s) filed on 10 March 2006 is/are: a)D accepted or b)D objected to by the Examiner.

Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1 .85(a).

Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
1 1 )□ The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.

Priority under 35 U.S.C. § 119

12)^ Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 1 19(a)-(d) or (f).
a)IElAII b)D Some * c)D None of:

1 .£3 Certified copies of the priority documents have been received.

2. Q Certified copies of the priority documents have been received in Application No. .

3. D Copies of the certified copies of the priority documents have been received in this National Stage

application from the International Bureau (PCT Rule 17.2(a)).
* See the attached detailed Office action for a list of the certified copies not received.

Attachment(s)

1 ) £3 Notice of References Cited (PTO-892) 4) □ Interview Summary (PTO-41 3)

2) □ Notice of Draftsperson's Patent Drawing Review (PTO-948) Paper No(s)/Mail Date. .

3) Information Disclosure Statement(s) (PTO/SB/08) 5 > □ Notice of Informal Patent Application
Paper No(s)/Mail Date 7 sheets . 6) □ Other: .

U.S. Patent and Trademark Office
PTOL-326 (Rev. 08-06)

Office Action Summary

Part of Paper No./Mail Date 20080201

Application/Control Number: Page 2

10/595,161

Art Unit: 1614

DETAILED ACTION
Status of the Claims and Examination
Claims 8-27 are pending and the subject of this Office Action.

Claim Rejections - 35 U.S.C. §112.1

The following is a quotation of the first paragraph of 35 U.S.C. §112:

The specification shall contain a written description of the
invention, and of the manner and process of making and using it, in
such full, clear, concise, and exact terms as to enable any person
skilled in the art to which it pertains, or with which it is most
nearly connected, to make and use the same and shall set forth the
best mode contemplated by the inventor of carrying out his
invention.

Claims 8-27 are rejected under 35 U.S.C. 1 12, first paragraph, as failing to comply with
the enablement requirement. The claim contains subject matter that was not described in the
specification in such a way as to enable one skilled in the art to which it pertains, or with which
it is most nearly connected, to make and/or use the invention.

Claim 8 is enabled for the treatment of the toxic effects of TNF-a, alcohol-induced
hepatitis, and cachexia by administering a compound of the instant invention. However, the
claimed prophylaxis of the toxic effects of TNF-a, alcohol-induced hepatitis, and cachexia is not
supported by the specification. As a result, the effect of performing the invention by one skilled
in the art would be that of undue experimentation.

Factors to be considered in determining whether a disclosure would require undue
experimentation have been summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986) and
reiterated by the Court of Appeals in In re Wands , 8 USPQ2d 1400 at 1404 (CAFC 1988). The

Application/Control Number: Page 3

10/595,161

Art Unit: 1614

factors to be considered in determining whether undue experimentation is required include: (1)
the quantity of experimentation necessary, (2) the amount or direction presented, (3) the presence
or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6)
the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the
breadth of the claims.

The Board also stated that although the level of skill in organic chemistry is high, the
results of experiments to discover treatments for the illnesses and conditions recited in claim 8, is
unpredictable. While all of the Wands factors are considered, a sufficient amount for a prima
facie case is discussed below.

The applicant has provided a number of working examples for treating patients with
disorders in claim 8. However, the applicant has failed to enable the prevention of these
disorders. Prophylaxis is generally defined as "the preventing of disease." Random House
Unabridged Dictionary, Random House, Inc. 2006. While there is support for the treatment of
the toxic effects of TNF-a, alcohol-induced hepatitis, and cachexia, the specification is void of
support for the prevention of the same.

As such, the art of the claimed invention lacks predictability because the claim as written
to include prevention of interstitial cystitis is drawn too broadly.

/

Double Patenting

The nonstatutory double patenting rejection is based on a judicially created doctrine
grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or

Application/Control Number: Page 4

10/595,161

Art Unit: 1614

improper timewise extension of the "right to exclude" granted by a patent and to prevent possible
harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection
is appropriate where the conflicting claims are not identical, but at least one examined
application claim is not patentably distinct from the reference claim(s) because the examined
application claim is either anticipated by, or would have been obvious over, the reference
claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re
Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225
USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re
Vogel 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163
USPQ 644 (CCPA 1969).

A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may
be used to overcome an actual or provisional rejection based on a nonstatutory double patenting
ground provided the conflicting application or patent either is shown to be commonly owned
with this application, or claims an invention made as a result of activities undertaken within the
scope of a joint research agreement.

Effective January 1, 1994, a registered attorney or agent of record may sign a terminal
disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR
3.73(b).

Claims 8-27 are rejected on the ground of nonstatutory obviousness-type double
patenting as being unpatentable over claim 31 of U.S. Patent Application No. 10-557,541.
Although the conflicting claims are not identical, they are not patentably distinct from each other
because the '541 patent application, like the instant invention, is drawn to a method of treating or

Application/Control Number: Page 5

10/595,161

Art Unit: 1614

preventing a pathologic disease or disorder. The methods articulated in claim 31 of the '541
application overlap in scope with the methods articulated in claims 8-27 of the instant invention,
because both utilize compounds with an identical core structure to treat the same family of
disease, cachexia in one instant, which is a known effect of cancer and a cell proliferative
disorder, of which cancer is known to be one.

This is a provisional rejection, because the claims have not, in fact, been patented.

In looking in continuity data, it is noted that applicant has numerous pending applications
encompassing the same or similar subject matter of the instant application. Applicant should
review all subject matter considered the same or similar, and submit the appropriate Terminal
Disclaimer(s). For example, pending patent applications with the same or similar subject matter
include, but are not limited to 10/595,126 and 1 1/402423.

Claim Rejections - 35 U.S.C. §102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the
basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless -

(a) the invention was known or used by others in this country, or patented or described in a printed publication in this
or a foreign country, before the invention thereof by the applicant for a patent.

(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed
in the United States before the invention by the applicant for patent or (2) a patent granted on an application for
patent by another filed in the United States before the invention by the applicant for patent, except that an
international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this
subsection of an application filed in the United States only if the international application designated the United
States and was published under Article 21(2) of such treaty in the English language.

Application/Control Number: Page 6

10/595,161

Art Unit: 1614

Claims 8-27 are rejected under 35 U.S.C. §102(a) and §102(e) as being anticipated
clearly by U.S. Patent Publication No. 2004/0077859 Al [hereinafter referred to as "Waer et
al"](Please consider the reference in its entirety).

Waer et al disclose novel pteridine compounds, with the core structure of

wherein X can represent an oxygen atom or a group with the formula NZ; Z is a group
independently defined as Rl or Z is hydrogen or the group NZ together with Rl is either
hydroxylamino or an optionally substituted heterocyclic group containing at least one nitrogen
atom; R3 together with R4 forms a homocyclic or heterocyclic radical (Pages 4 to 5, para. 23);
and R4 can be hydrogen, halogen, etc (Page 3, para. 22).

Waer et al also teach pharmaceutical^ acceptable addition salts stereoisomers and
dihydro or tetrahydropterdine derivates of the above structure (Page 5, para. 24). These
compounds can be used to treat or prevent hepatitis B-, C-, and D- (Page 18, paras 149-153 and
155). A specific example of a compound representative of the above formula is 2-amino-4-
piperazino-6-(4-methoxyphenyl) pteridine (Page 22, para. 218).

In view of the foregoing, claims 8-27 are clearly anticipated by Waer et al.

Claim Rejections - 35 U.S.C. §103

The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness-
rejections set forth in this Office action:

Application/Control Number:

10/595,161

Art Unit: 1614

Page 7

(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in
section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are
such that the subject matter as a whole would have been obvious at the time the invention was made to a person
having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the
manner in which the invention was made.

This application currently names joint inventors. In considering patentability of the
claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various
claims was commonly owned at the time any inventions covered therein were made absent any
evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out
the inventor and invention dates of each claim that was not commonly owned at the time a later
invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) '
and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).

Claims 8-27 are rejected under 35 U.S.C. 103(a) as being obvious over Iwagaki, H., et al,
"Decreased Serum Tryptophan In Patients With Cancer Cachexia Correlates With Increased
Serum Neopterin," Immunological Investigations, Vol. 24, Issue 3, pages 467-478
(1995)[Iwagaki, et al"](Please consider the reference in its entirety.

Iwagaki et al disclose the following chemical structure for neopterin

TRP IN PATIENTS WITH CANCER CACHEXIA 469

and teaches that neopterin [hereinafter referred to as "NPT"] comes from activated macrophages
that are activated by tumor-sensitized T cells via gamma interferon (IFN-y) (See Abstract; Page

Application/Control Number: Page 8

10/595,161

Art Unit: 1614

468, lines 14-20) and that NPT is released from cells based on the interaction of T-cells and
macrophages (Page 469, Figure 2). Iwagaki et al also teach that an increase in NPT production
and presence in tumor cells is indicative of cancer cachexia (Page 468, lines 20-26; Page 471,
lines 1-3; Page 473, lines 7-13), and that presence of NPT has an inverse relationship with the
presence of tryptophan (Page 473, lines 7-13). Thus, an increase in the levels of tryptophan
would reflect a decrease in the levels of NPT, thereby effectively treating and potentially
preventing cachexia. (Page 476, Figure 5 and text thereafter).

NPT is an obvious variation of the core structure of the instant invention, differing
mainly by the functional group attached NPT's position one and the position of the oxygen
substituent at position four rather than, for example, a methyl ether, as contemplated by the
instant invention. Based on the examples below, as disclosed in Brown, D.J., et al, "Pterdine
Studies. Part XIV. Methylation of 2-Amino-4-hydroxypterdine and Related Compounds," J.
Amer. Chem. Soc, Vol. 869, pages 4413-4420 (1961), as early as 1961 this core structure was
known and with varying substitutions, such as oxygen, hydroxyl, methyl, amines, and methyl

(VI) (VJ1) (VII!) (IX)

Application/Control Number:

10/595,161

Art Unit: 1614

Page 9

Me Me Me

(X) (XI) (XII) IXIIJ)

ether, at various positions on the ring in question. For example, structure 12 above shows the
core structure with a reactive oxygen site for which the methyl group could easily attach to
stabilize the compound, which would yield the compound of the instant invention. The
suggestion therefore, is that these reactive sites are not necessarily critical for to functionality of
the compound as a whole.

In light of the foregoing, it would have been prima facie obvious to one of ordinary skill
modify the teachings of Iwagaki et al by substituting the compound of the instant invention and
concluding that the same would be useful in the treatment of cachexia.

Conclusion

No claims are allowed.

Any inquiry concerning this communication or earlier communications from the
examiner should be directed to Alicia Hughes whose telephone number is 571-272-6026. The
examiner can normally be reached from 9:00 A.M. until 5:00 P.M. on Monday through Friday.

If attempts to reach the examiner by telephone are unsuccessful, the examiner's
supervisor, Ardin Marschel, can be reached at 571-272-0718. The fax number for the
organization where this application or proceeding is assigned is 571-273-8300.

Application/Control Number:

Page 10

10/595,161
Art Unit: 1614

Information regarding the status of an application may be obtained from the Patent
Application Information Retrieval (PAIR) system. Status information for published applications
may be obtained from either Private PAIR of Public PAIR. Status information for unpublished
applications is available through Public PAIR only. For information about the PAIR system, see
http://pair-direct-uspto.gov . Should you have questions on access to the Private PAIR system,
contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like
assistance from a USPTO Customer Service Representative or access to the automated
information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.